Modulation of intestinal microbiota in pre-diabetes and type 2 diabetes

Abstract

Provided herein are methods for modulating the intestinal microbial profile and for reducing intestinal dysbiosis in type 2 diabetic or pre-diabetic subjects, comprising administering metformin or a derivative or salt thereof and one or more probiotic microorganisms selected from Lactobacillus plantarum, Lactobacillus bulgaricus, Lactobacillus gasseri, Bifidobacterum breve, Bifidobacterium animalis subsp. lactis, Bifidobacterium bifidum, Streptococcus thermophilus and Saccharomyces boulardii. Also provided are methods for treating type 2 diabetes or an associated metabolic complication or condition and for delaying the onset of type 2 diabetes in pre-diabetic subjects, comprising administering one or more probiotic microorganisms selected from Lactobacillus plantarum, Lactobacillus bulgaricus, Lactobacillus gasseri, Bifidobacterum breve, Bifidobacterium animalis sub sp. lactis, Bifidobacterium bifidum, Streptococcus thermophilus and Saccharomyces boulardii.

1 . A method for modulating the intestinal microbial profile in a type 2 diabetic or pre-diabetic subject, the method comprising administering to the subject metformin or a derivative or salt thereof and one or more probiotic microorganisms selected from  Lactobacillus plantarum, Lactobacillus bulgaricus, Lactobacillus gasseri, Bifidobacterum breve, Bifidobacterium animalis  subsp.  lactis, Bifidobacterium bifidum, Streptococcus thermophilus  and  Saccharomyces boulardii , whereby the modulation of the intestinal microbial profile resulting from said administration comprises a decrease in abundance of pathogenic bacteria or bacteria that do not tolerate the host and/or an increase in the abundance of bacteria that tolerate the host. 
     
     
         2 . A method according to  claim 1 , wherein the intestinal microbial profile is determined by sequencing of faecal DNA from one or more faecal samples obtained the subject. 
     
     
         3 . A method according to  claim 1  or  2 , wherein modulation of the intestinal microbial profile comprises an increase in abundance of one or more  Bifidobacterium  spp.,  Phascoarctobacterium  spp. and/or  Akkermansia  spp. 
     
     
         4 . A method according to any one of  claims 1  to  3 , wherein modulation of the intestinal microbial profile comprises a decrease in abundance of one or more  Roseburia  spp. 
     
     
         5 . A method for reducing intestinal dysbiosis in a type 2 diabetic or pre-diabetic subject, the method comprising administering to the subject metformin or a derivative or salt thereof and one or more probiotic microorganisms selected from  Lactobacillus plantarum, Lactobacillus bulgaricus, Lactobacillus gasseri, Bifidobacterum breve, Bifidobacterium animalis  subsp.  lactis, Bifidobacterium bifidum, Streptococcus thermophilus  and  Saccharomyces boulardii.    
     
     
         6 . A method according to any one of  claims 1  to  5 , wherein the metformin or derivative or salt thereof is administered in conjunction with a multi-strain probiotic combination comprising  Lactobacillus plantarum, Lactobacillus bulgaricus, Lactobacillus gasseri, Bifidobacterum breve, Bifidobacterium animalis  subsp.  lactis, Bifidobacterium bifidum, Streptococcus thermophilus  and  Saccharomyces boulardii.    
     
     
         7 . A method according to any one of  claims 1  to  6 , wherein the metformin or derivative or salt thereof and the one or more probiotic microorganisms or the multi-strain probiotic combination are administered simultaneously or sequentially. 
     
     
         8 . A method according to any one of  claims 1  to  6 , wherein the metformin or derivative or salt thereof and the one or more probiotic microorganisms or the multi-strain probiotic combination are formulated in the same composition. 
     
     
         9 . A method for treating type 2 diabetes or a metabolic complication or condition associated therewith in a subject, the method comprising administering to the subject one or more probiotic microorganisms selected from  Lactobacillus plantarum, Lactobacillus bulgaricus, Lactobacillus gasseri, Bifidobacterum breve, Bifidobacterium animalis  subsp.  lactis, Bifidobacterium bifidum, Streptococcus thermophilus  and  Saccharomyces boulardii.    
     
     
         10 . A method according to  claim 9 , wherein treating the type 2 diabetes or metabolic complication or condition associated therewith comprises decreasing glycosylated haemoglobin (HbA1c) levels, reducing BMI, improving insulin sensitivity, or reducing insulin resistance. 
     
     
         11 . A method for delaying or inhibiting the onset of type 2 diabetes in a pre-diabetic subject, the method comprising administering to the subject one or more probiotic microorganisms selected from  Lactobacillus plantarum, Lactobacillus bulgaricus, Lactobacillus gasseri, Bifidobacterum breve, Bifidobacterium animalis  subsp.  lactis, Bifidobacterium bifidum, Streptococcus thermophilus  and  Saccharomyces boulardii.    
     
     
         12 . A method according to  claim 11 , wherein delaying or inhibiting the onset of type 2 diabetes comprises decreasing glycosylated haemoglobin (HbA1c) levels, reducing BMI, improving insulin sensitivity, or reducing insulin resistance. 
     
     
         13 . A method according to any one of  claims 9  to  12 , wherein the subject is administered a multi-strain probiotic combination comprising  Lactobacillus plantarum, Lactobacillus bulgaricus, Lactobacillus gasseri, Bifidobacterum breve, Bifidobacterium animalis  subsp.  lactis, Bifidobacterium bifidum, Streptococcus thermophilus  and  Saccharomyces boulardii.    
     
     
         14 . A method according to any one of  claims 9  to  13 , wherein the subject is also administered metformin or a derivative or salt thereof. 
     
     
         15 . A composition for treating type 2 diabetes or a metabolic complication or condition associated therewith, for delaying or inhibiting the onset of type 2 diabetes, or for modulating the intestinal microbiota in a type 2 diabetic or pre-diabetic subject, the composition comprising metformin or a derivative or salt thereof and one or more probiotic microorganisms selected from  Lactobacillus plantarum, Lactobacillus bulgaricus, Lactobacillus gasseri, Bifidobacterum breve, Bifidobacterium animalis  subsp.  lactis, Bifidobacterium bifidum, Streptococcus thermophilus  and  Saccharomyces boulardii.